Background:  HCV is a major morbidity in HIV-infected subjects. Treatment of HCV in co-infected patients has low success and high intolerability. We compared the safety, tolerability, and efficacy of interferon (IFN) + ribavirin (RBV) and PEG-IFN + RBV, in co-infected subjects. 

Methods:  This was a randomized, multicenter, open-label trial. Inclusion criteria for HCV:  detectable HCV RNA and abnormal liver histology;  for HIV:  CD4 >100 and HIV-1 RNA <10,000 on stable ART, or CD4  >300 off ART. Subjects were randomized to IFN-a-2a 6 MIU tiw x 12 weeks, then 3 MIU x 36 weeks, or PEG-IFN--2a 180 mcg qwk for 48 weeks. Each arm received RBV beginning at 600 mg/day, escalating to a maximum of 1 g/day.  Primary endpoint was HCV RNA <60 IU by Roche Amplicor assay at week 24. Virologic responders (VR) continued treatment until week 48. Virologic nonresponders (VNR) underwent liver biopsy (bx), with continuation of treatment to week 48 only for those with a ≥2-point drop in total hepatic activity index (HAI).   

Results:  133 eligible subjects were randomized.  Gender, age, ethnicity, HCV RNA, HCV genotype, undetectable HIV-1 RNA, CD4, Karnofsky score (KS), fibrosis, and total HAI score at entry were not significantly different between arms.  By intention to treat analysis, PEG had significantly higher week 24 VR (44% vs 15%, p = 0.0003). Multivariate models showed PEG, white race, KS=100, and low fibrosis to be jointly associated with VR. Among VNR undergoing week 24 bx, 15/37 (40%) in the IFN and 6/23 (26%) in the PEG group experienced histologic improvement. Total CD4 fell in both arms (-111/PEG –77/IFN if entry CD4 <700; -390 vs -149 if entry CD4 >700), but percentage of CD4 and HIV-1 RNA detectability did not change.   Although the PEG group experienced more grade-4 toxicity events (17 vs 5, p = 0.004), premature treatment discontinuation was not different between the 2 groups (15% vs 12%).

Conclusions:  PEG-IFN--2a + RBV is associated with a superior VR in HCV/HIV.  Both treatments were well-tolerated. Over a third of VNR who underwent bx had histologic response, suggesting benefits without VR.  Although total CD4 fell with each arm, no adverse effects on HIV control were seen.  These data demonstrate a significant benefit for HCV combination therapy in HCV/HIV co-infection. Long-term response and safety will be addressed with trial completion.